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The pharmacokinetics of racemic MDPV and its (R) and (S) enantiomers in female and male rats.
Hambuchen, Michael D; Hendrickson, Howard P; Gunnell, Melinda G; McClenahan, Samantha J; Ewing, Laura E; Gibson, Dillon M; Berquist, Michael D; Owens, S Michael.
Afiliación
  • Hambuchen MD; Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Electronic address: HambuchenMichaelD@uams.edu.
  • Hendrickson HP; Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • Gunnell MG; Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • McClenahan SJ; Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • Ewing LE; Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • Gibson DM; Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • Berquist MD; Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • Owens SM; Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Drug Alcohol Depend ; 179: 347-354, 2017 10 01.
Article en En | MEDLINE | ID: mdl-28844011
BACKGROUND: These studies investigated the serum pharmacokinetic (PK) profile of racemic (3,4)-methylenedioxypyrovalerone [(R,S)-MDPV)] and its (R)- and (S)-enantiomers in female and male Sprague Dawley rats. METHODS: Intravenous (R,S)-MDPV (3 and 5.6mg/kg) and single enantiomer of (R)- and (S)-MDPV (1.5mg/kg) were administered to both sexes for PK studies. Intraperitoneal (ip) bioavailability was determined at 3mg/kg (R,S)-MDPV. Locomotor activity studies were conducted after ip treatment with saline and 0.3-5.6mg/kg of (R,S)-MDPV. RESULTS: PK values after iv (R,S)-MDPV showed a significant (p<0.05) sex-dependent differences in the volume of distribution at steady state (Vdss) for (R)- and (R,S)-MDPV at both (R,S)-MDPV doses. The female S/R enantiomeric ratios for area under the concentration time curve (AUCinf) and clearance were significantly lower and higher, respectively, than values determined in males. Importantly, there was no evidence of in vivo inversion of (R)-MDPV or (S)-MDPV to its antipode. There were, however, significant sex-dependent differences in volume of distribution after administration of the (R)-enantiomer. Bioavailability studies of ip (R,S)-MDPV showed greater variability and significantly greater bioavailability in male rats. Accordingly, there was a significantly greater maximal distance traveled measurement in male rats at a 3.0mg/kg dose. CONCLUSION: PK sex differences in (R,S)-MDPV and enantiomers were most apparent in volume of distribution, which could be caused by differences in drug blood and tissue protein binding. The increased magnitude and variance in ip bioavailability in male compared to female rats could lead to sex-dependent differences in the pharmacological action caused by active enantiomer (S)-MDPV.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirrolidinas / Benzodioxoles / Locomoción Límite: Animals Idioma: En Revista: Drug Alcohol Depend Año: 2017 Tipo del documento: Article Pais de publicación: Irlanda
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirrolidinas / Benzodioxoles / Locomoción Límite: Animals Idioma: En Revista: Drug Alcohol Depend Año: 2017 Tipo del documento: Article Pais de publicación: Irlanda